Epstein Barr virus (EBV) is the cause of infectious mononucleosis and is associated with a number of cancers including Burkitt lymphomas and lymphomas in transplant recipients. We have been studying EBV DNA in the blood of transplant recipients or other immunocompromised persons, patients with chronic active EBV disease, and patients with diseases in which EBV may be a cofactor. EBV establishes latency in B cells in the blood and the latent EBV load in healthy individuals is generally stable over time maintaining a set-point. To determine if the EBV viral load changes after long-term antiviral therapy in healthy individuals, this year we treated volunteers with either valacyclovir or no antiviral therapy for 1 year and measured the amount of EBV DNA in B cells every 3 months with a novel ultrasensitive assay. The assay we developed measures EBV DNA copies in purified B cells after limiting dilution and a mathematical (Poisson distribution) analysis of the results. The number of EBV-infected B cells decreased in subjects receiving valacyclovir (half life of 11 months, p=0.02), but not in controls (half life of 31 years, p=0.86). In contrast, the number of EBV DNA copies per B cell remained unchanged in both groups (p=0.62 and p=0.92, for the control and valacyclovir groups, respectively). Therefore, valayclovir reduces the frequency of EBV-infected B cells when administered over a long period of time and in theory might allow eradication of EBV from the body if reinfection does not occur.